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Biomedical subjects

Toshiyuki Takeshita

Publications and source records attributed to Toshiyuki Takeshita.

At least 19 recordsLinked to original sources
PubMed2006

The cytotrophoblast layer of human chorionic villi becomes thinner but maintains its structural integrity during gestation.

Chorionic villi in the human placenta serve as essential structures in fetomaternal exchanges. According to the embryology and placentology literature, during the first trimester, the cytotrophoblast (CTB) layer that is subjacent to the syncytiotrophoblast (STB) and supported by a basal lamina is nearly complete, but later, it becomes discontinuous. In the present study, we investigated the structural integrity of the CTB layer in the normal villous tree by advanced microscopy techniques using an antibody to hepatocyte growth factor (HGF) activator inhibitor type 1 (SPINT1), a potent inhibitor of HGF activators expressed exclusively on villous CTB. In full-term placenta, the cell surface of the CTB layer was spread over the basal lamina but was not interrupted. Morphometric analysis showed that throughout the villous tree, 80% of the continuity of the CTB layer of full-term placenta and 90% of that of first-trimester placenta were preserved. Gestation was accompanied by unique structural change in the basal domain of the trophoblast layer. The initially cuboidal-shaped CTB cells were transformed to flat cells with many cellular processes that, together with those of the adjacent STB, eventually covered the trophoblast basal lamina in a complex network of interdigitations. In addition, the expression levels of SPINT1, ST14, HGF, and MET mRNAs in the villous tree increased over the course of gestation. These results suggest that the structural integrity of the SPINT1-positive CTB layer may play an important role in villous differentiation and in maintenance of the villous tree via the HGF signaling system during gestation.

Basement Membrane↗
PubMed2006

Prediction of HELLP syndrome with assessment of maternal dual hepatic blood supply by using Doppler ultrasound.

OBJECTIVE: Early structural and functional changes in the systemic vasculature have been proposed to play a major pathogenetic role in HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Our objective was to assess whether the evaluation of maternal hepatic blood supply is instructive to the prediction of onset of HELLP syndrome. DESIGN: Prospective observation study. POPULATION: Fifty-eight women with severe preeclampsia and 60 healthy pregnant controls at 25-36 weeks gestation. METHODS: Angle-corrected time-averaged flow velocity and the cross-sectional area of common hepatic artery and portal vein were measured by using Doppler ultrasonography in 58 women with severe preeclampsia and in 60 healthy pregnant controls at 25-36 weeks gestation. Intravascular flow volumes were calculated from the product of the time-averaged velocity and the cross-sectional area. The total liver blood flow was taken as the sum of flow volumes in the hepatic artery and portal vein. RESULTS: The total liver blood flow decreased significantly to about 40% of control in 9 women with severe preeclampsia who developed HELLP syndrome within 4 days after the examination, but not in 49 women with severe preeclampsia without HELLP syndrome. CONCLUSION: The results indicated that the decrease in dual hepatic blood supply preceded the onset of HELLP syndrome.

Adult↗
PubMed2006

Ultrahigh-resolution immunofluorescence microscopy using ultrathin cryosections: subcellular distribution of caveolin-1alpha and CD31 in human placental endothelial cells.

We compared the z-axis resolutions achieved by immunofluorescence (IF) microscopic imaging of tissue sections of different thicknesses (ultrathin cryosections, optical sections of cryostat sections and conventional cryostat sections). We used these images to determine the distribution of caveolin-1alpha (CAV-1alpha) and CD31 in endothelial cells of full-term, human placenta. Anti-CAV-1alpha antibody was used to visualize caveolae, which are among the smallest organelles. By using ultrathin cryosections as substrates for IF microscopy, we were able to resolve discrete caveolae that were primarily present immediately beneath the endothelial cell surface. In contrast, neither conventional nor confocal images from cryostat sections were able to resolve individual caveolae, despite dramatic reductions in the confocal image degradation that arises from out-of-focus fluorescence signals. Anti-CD31 antibody labeled the endothelial cell surface exclusively. Quantitative analysis of ultrathin cryosections showed that about 2.5 times more CD31 was expressed on the luminal surface of cells than on the abluminal surface. Our results demonstrate that ultrathin cryosections can serve as excellent substrates for ultrahigh-resolution IF microscopy.

Caveolae↗
PubMed2006

Incidence and risk factors for severe perineal laceration after vaginal delivery in Japanese patients.

OBJECTIVE: The aim of this study was to assess the frequency of severe perineal lacerations defined as either third- or fourth-degree lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors in Japanese patients. MATERIALS AND METHODS: An electronic audit of the perinatal database at the Tama-Nagayama Hospital of Nippon Medical School and Yamaguchi Hospital from 1997 through 2004 was completed. Singleton vaginal vertex deliveries were analyzed for potential risk factors using univariate and multivariate logistic regression analysis. RESULTS: From the database, 7,946 deliveries were identified, with 135 deliveries resulting in severe lacerations (1.7%). In the multivariate logistic regression analysis, severe lacerations were associated significantly with primiparous (odds ratio, 4.36; 95% CI, 2.17-9.57), oxytocin use (odds ratio, 2.19; 95% CI, 1.27-3.73), midline episiotomy (odds ratio, 4.68; 95% CI, 2.09-11.55), forceps-assisted delivery (odds ratio, 7.11; 95% CI, 1.95-20.59), vacuum-assisted delivery (odds ratio, 5.93; 95% CI, 3.38-10.36), and shorter attendant experience (odds ratio, 2.88; 95% CI, 1.12-9.81). CONCLUSIONS: The present study demonstrated that operator factors, such as midline episiotomy, oxytocin use, assisted delivery and attendant experience, are independent risk for severe perineal lacerations after vaginal delivery in Japanese patients. The results suggest that midline episiotomy and assisted vaginal delivery, especially forceps-assisted delivery should be avoided in patients who are being delivered of a first child whenever possible.

Adult↗
PubMed2006

Effect of sera on the adhesion of natural killer cells to the endothelium in severe pre-eclampsia.

OBJECTIVE: To investigate the effect of serum on the interaction between natural killer (NK) cells and endothelial cells in pre-eclampsia. METHODS: Seven severely pre-eclamptic patients, five normal pregnant women, and four normal non-pregnant women were included in this study. Freshly isolated NK cells labeled with Chromium-51 were incubated on an endothelial cell monolayer in the presence of patient serum. In regard to the characteristics of adhesive molecules, the endothelial cells were blocked by monoclonal antibodies (mAbs) to intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1); the NK cells were blocked by mAbs to leukocyte function-associated antigen (LFA-1) and very late antigen-4 (VLA-4) before co-incubation. After incubation, the adherent cells were solubilized with 1% Triton X. The lysates were collected and counted in a gamma counter. RESULTS: The adhesion of NK cells to the endothelium in the normal pregnancy group decreased significantly in comparison to the non-pregnant group (7%vs 72%; P < 0.01). Adhesion in the severe pre-eclamptic group was significantly higher in comparison to the normal pregnant group (44%vs 7%; P < 0.01). The blocking percentages of mAbs on NK adhesion in the severe pre-eclampsia group were 49 +/- 4% to LFA-1, 61 +/- 48%, 67 +/- 39% to VLA-4, ICAM-1, and 68 +/- 7% to VCAM-1. CONCLUSION: Sera from normal pregnant women suppress the adhesion between NK cells and endothelial cells, whereas the suppressive effect of sera from pre-eclamptic patients has a diminished affect.

Adult↗
PubMed2006

Effect of first-trimester ultrasound examination for chromosomal aberrations in women undergoing amniocentesis.

OBJECTIVE: The purpose of this study was to assess the effect of first-trimester ultrasound examination for chromosomal aberrations in women who underwent amniocentesis. METHODS: To evaluate trends in the indications of amniocentesis and the number of chromosomal aberrations, we reviewed all amniotic fluid samples from genetic amniocentesis processed by the Tama-Nagayama Hospital of Nippon Medical School from 1991 through 2005. The referral indications included first-trimester abnormal ultrasound finding. RESULTS: A total of 1,054 women underwent genetic aminiocentesis in the first- to early second-trimester, and 1,063 amniotic samples were processed. The overall rate of chromosomal aberrations was 3.3% (35 of 1,063 samples), and the rate of aberrations remained unchanged during the study period. The number of cases with abnormal ultrasound finding increased from 5 (1.1%) in the first 5-year period to 46 (19.4%) in the last 5-year period (p<0.01). In contrast, the number of amniotic fluid samples per year tended to decline during the study period. CONCLUSION: First-trimester ultrasound examination had a significant effect on our amniocentesis cases. The application of first-trimester ultrasound examination may be associated with a lower rate of invasive genetic testing.

Amniocentesis↗
PubMed2005

Relation between plasma adenosine and serum TSH levels in women with hyperemesis gravidarum.

INTRODUCTION: This study investigated the relation between adenosine and thyroid function associated with hyperemesis gravidarum. METHODS: We examined 84 Japanese singleton pregnant women with an average age of 33.0+/-5.8 years at 9-12 weeks gestation being managed at our hospital. The patients were divided into three groups according to the severity of emesis: (1) those with hyperemesis gravidarum (nausea and vomiting with weight loss >5%, n=13), (2) those with emesis (nausea and vomiting with weight loss <5%, n=31), and (3) those with no symptoms as a control (n=40). RESULTS: The average serum TSH levels in the emesis and hyperemesis groups were significantly higher than that in the control group (P<0.05). The average plasma adenosine level in the hyperemesis group was significantly higher than those in the control pregnant and emesis groups (P<0.05). There were no significant differences in plasma adenosine levels between the control pregnant and emesis groups. The serum TSH level showed significant correlations with weight loss (%) and plasma adenosine levels (P<0.05). CONCLUSIONS: Our findings support the possible role of adenosine in counteracting the further progression of hyperemesis gravidarum associated with gestational thyrotoxicosis.

Adenosine↗
PubMed2005

Maternal basal metabolic rate in twin pregnancy.

OBJECTIVE: This study examined the basal metabolic rate in patients with twin pregnancies and compared the results with those of singleton pregnancies and non-pregnant women. METHODS: In 15 non-pregnant women, 14 patients with twin and 25 patients with singleton pregnancies, the resting energy expenditure was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The averaged resting energy expenditure in patients with twin pregnancy was 1,636 +/- 174 kcal/day, significantly higher than that in patients with singleton pregnancy (1,456 +/- 158 kcal/day; p < 0.05). Both of these levels are significantly higher than those in non-pregnant women (1,228 +/- 132 kcal/day; p < 0.05). CONCLUSION: Our results indicate that the estimated increased metabolic demands in patients during the third trimester of twin pregnancy are about 10% higher than those in women with singleton pregnancy. A prospective clinical study concerning nutrition counseling is needed.

Adult↗
PubMed2005

Increased level of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery.

OBJECTIVE: The objective of this study was to explore whether increased levels of granulocyte elastase in cervical secretion is an independent predictive factor for preterm delivery before 34 weeks of gestation in the patient with preterm labor. METHODS: One hundred and sixty-one women with preterm labor at 22-28 weeks of gestation were enrolled prospectively. The level of granulocyte elastase in cervical secretions was measured by immunoassay, vaginal secretions were collected for the microscopic evaluation of Gram-stained smears, and the uterine cervix was assessed by transvaginal ultrasonography. RESULTS: Nineteen of 161 patients (12%) delivered before 34 weeks of gestation. Granulocyte elastase assessment had a sensitivity, specificity, positive predictive value, and negative predictive value for preterm delivery of 53, 75, 22 and 92%, respectively. A positive elastase assessment was associated with a relative risk for preterm delivery of 2.9 (95% CI 1.3-6.6), whereas a positive bacterial vaginosis assessment and shorter cervical length less than 25 mm demonstrated a relative risk of 1.9 (95% CI 0.8-4.6) and 1.5 (95% CI 0.6-5.0), respectively. CONCLUSION: The present study demonstrates that the risk of spontaneous preterm delivery before 34 weeks of gestation is increased in the women with preterm labor who are found to have an increased level of granulocyte elastase in cervical secretions.

Adult↗
PubMed2005

Resting oxygen consumption in patients with twin pregnancy.

OBJECTIVE: This study examined the resting oxygen consumption in patients with a twin pregnancy and compared the results with those of singleton pregnancies. METHODS: In 15 patients with a twin and 26 patients with a singleton pregnancy, the resting oxygen consumption was measured using an open-circuit ventilatory system during the third trimester of pregnancy. RESULTS: The average resting oxygen consumption in patients with a twin pregnancy was 231+/-25 ml/min, significantly higher than that in patients with a singleton pregnancy (209+/-24 ml/min, P<0.05). CONCLUSION: Our results indicate an estimated increase in metabolic rate in patients during the third trimester of a twin pregnancy compared with those with a singleton pregnancy.

Adult↗
PubMed2005

Maternal treatment with MCI-186 does not improve delayed deterioration of cellular bioenergetic state and mitochondrial activity following transient intrauterine ischemia in the fetal rat brain.

The mitochondrial respiratory activities and energy metabolism in the fetal rat brain were measured at the end of 30 minutes of intrauterine ischemia and after 2 and 4 hours of recirculation. The transient ischemia was associated with a delayed deterioration of cellular bioenergetic state and mitochondrial activities. The deterioration was not prevented by a free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), given immediately after recirculation.

Animals↗
PubMed2005

Gasless laparoscopic surgery using a new intra-abdominal fan retractor system: an experience of 500 cases.

AIM: The aim of this study is to report the feasibility of a newly developed intra-abdominal fan retractor system for use in gynecologic laparoscopic surgery. METHODS: Five hundred women undergoing gasless laparoscopic surgery using the abdominal wall lifting device were included in the study. The intraoperative and postoperative courses, and complications were examined. RESULTS: The intra-abdominal retractor system provided adequate exposure in all cases, except for one patient with morbid obesity. Neither the presence of the intra-abdominal retractor blades nor the mechanical arm interfered with the placement of instruments during surgery. No complications related to the use of gasless laparoscopy were encountered in this study period. CONCLUSION: The new intra-abdominal fan retractor system is feasible in gynecologic laparoscopic surgery.

Feasibility Studies↗
PubMed2005

Up-regulation of growth factor receptor-bound protein 10 in cervical squamous cell carcinoma.

The Grb10 gene on chromosome 7p11.2-p12 belongs to a family of adapter proteins known to interact with a number of receptor tyrosine kinases, such as EGF, ErbB2/Her2, platelet-derived growth factor (PDGF), IGF-I receptors and vascular endothelial growth factor (VEGF) receptor, KDR (kinase insert domain containing receptor). In addition to receptor tyrosine kinases, Grb10 has also been found to interact with non-receptor tyrosine kinases such as Tec and Bcr-Abl, other cellular signaling molecules such as Raf-1, and the mitogen-activated protein (MAP) kinase, MEK. We demonstrated increased expression of Grb10 mRNA in more than one half of primary cervical squamous cell cancers (12 of 15 cases) when compared to corresponding non-cancerous uterine squamous cell tissues. In addition, immunohistochemical staining demonstrated that the Grb10 protein was prominent in the cytoplasm of cancer cells, whereas it was unreactive in the surrounding normal cervical squamous cells. In addition, its interruption by siRNA exhibited marked cell growth inhibition. These data indicate that amplification and increased expression of the Grb10 gene may play a role in the development of a portion of human cervical squamous cell cancer.

Adult↗
PubMed2004

Transmission of macrophage-tropic HIV-1 by breast-milk macrophages via DC-SIGN.

Recent findings suggest that macrophage-tropic human immunodeficiency virus type 1 (HIV-1) produced in colostrum/early breast milk may hold a clue to determine the mechanisms of transmission of HIV-1 via breast-feeding. Here, we show that the majority of CD4(+) cells in the colostrum are CD14(+) macrophages expressing both chemokine receptors and DC-SIGN, a dendritic cell-specific receptor for HIV-1. The R5-type macrophage-tropic HIV-1 isolate NL(AD8) infected such breast-milk macrophages and caused them to secrete virus particles efficiently; however, the secreted virions showed only a weak transmissibility to their susceptible target, MAGIC-5 cells. When stimulated with interleukin-4, the breast-milk macrophages demonstrated a striking enhancement of expression of DC-SIGN and showed a strong capacity to transmit NL(AD8) virions to MAGIC-5 cells, which was specifically blocked by anti-DC-SIGN-specific antibody. These results suggest that HIV-1 virions captured by DC-SIGN, but not secreted cell-free virions, may be more efficiently transmitted to other compartments, such as the gastrointestinal tract, through acidic gastric juice.

Adult↗
PubMed2004

Role of mitochondrial permeability transition in fetal brain damage in rats.

Recirculation after transient in utero ischemia has previously been found to be accompanied by delayed deterioration of cellular bioenergetic state and of mitochondrial function in the fetal rat brain. Our objective was to assess whether the delayed deterioration is a result of the activation of mitochondrial permeability transition which is observed ultrastructurally as mitochondrial swelling. The respiratory activities and ultrastructure of isolated mitochondria and the cellular bioenergetic state in fetal rat brain were examined at the end of 30 minutes of in utero ischemia and after 1, 2, 3 and 4 hours of recirculation. Cyclosporin A, a potent and virtually specific mitochondrial permeability transition blocker, or vehicle was administered 1 hour after recirculation. In the vehicle-treated animals, the transient ischemia was associated with a delayed deterioration of cellular bioenergetic state and mitochondrial activities at 4 hours of recirculation. The number of swollen mitochondria increased markedly after 4 hours of recirculation. The deterioration and the swelling were prevented by cyclosporin A. The present study indicates that cyclosporin A treatment improves recovery of fetal brain energy metabolism and inhibits the mitochondrial swelling after transient in utero ischemia. The results suggest that mitochondria and mitochondrial permeability transition may be involved in the development of ischemic brain damage in the immature rat.

Animals↗
PubMed2004

Diagnosis and treatment of recurrent miscarriage associated with immunologic disorders: Is paternal lymphocyte immunization a relic of the past?

Miscarriage is the most common complication of human pregnancy. Although the causes of recurrent miscarriage (RM) are various, immunologic aberrations between mother and fetus might be one of the causes of miscarriage. Immune responses fall into two categories: autoimmune and alloimmune. Currently, no appropriate diagnostic method has been established to identify alloimmune causes. We observed that NK cell activity in women with RM was higher than that in women without a history of miscarriage. Functional or quantitative analysis of NK cells could be used to identify alloimmune causes. Paternal lymphocyte immunization has been the most widely used treatment for alloimmune-mediated miscarriages. However, the latest Cochrane review by Scott reached the current conclusion that lymphocyte immunization therapy provided no significant beneficial effect over placebo in preventing further miscarriage. Approximately 70% of Japanese university hospitals are still performing paternal lymphocyte immunization. Is paternal lymphocyte immunization a relic of the past? Randomized controlled trials based on adequate patient selection in Japan should provide an answer to this question.

Abortion, Habitual↗
PubMed2004

Prognostic significance of Ki-67 antigen immunostaining (MIB-1 monoclonal antibody) in ovarian cancer.

OBJECTIVE: To assess the potential usefulness of Ki-67 antigen expression as a predictor of outcome in ovarian cancer through the analysis of MIB-1 monoclonal antibody reactivity. METHODS: Cell proliferation and clinicopathologic variables were assessed in 26 patients with primary epithelial ovarian cancer who had undergone exploratory laparotomy. The expression of primary tumor proliferation related to Ki-67 antigen was immunohistochemically evaluated by MIB-1 monoclonal antibody. RESULTS: The value of Ki-67 labeling index (LI) ranged between 0 and 92.6% with a mean of 48.9%. Ki-67 LI correlated well with the mitotic index, but not the histological subtype. Ki-67 LI of more than 40%was defined as a higher proliferating tumor by a receiver operating characteristic curve analysis. Higher proliferating tumors were identified in 14 patients (54% of all subjects). The patients with higher proliferating tumors had a statistically significantly worse prognosis compared with those with lower proliferating tumors (p<0.001). CONCLUSIONS: The present study demonstrates that the proliferating index detected by Ki-67 antigen immunostaining is a useful factor for predicting the survival of patients with ovarian cancer.

Adult↗